Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes.
Strong epidemiologic evidence suggests an association between Alzheimer disease (AD) and type 2 diabetes. To determine if amyloid beta (Abeta) and hyperphosphorylated tau occurs in type 2 diabetes, pancreas tissues from 21 autopsy cases (10 type 2 diabetes and 11 controls) were analyzed. APP and tau mRNAs were identified in human pancreas and in cultured insulinoma beta cells (INS-1) by RT-PCR. Prominent APP and tau bands were detected by Western blotting in pancreatic extracts. Aggregated Abeta, hyperphosphorylated tau, ubiquitin, apolipoprotein E, apolipoprotein(a), IB1/JIP-1 and JNK1 were detected in Langerhans islets in type 2 diabetic patients. Abeta was co-localized with amylin in islet amyloid deposits. In situ beta sheet formation of islet amyloid deposits was shown by infrared microspectroscopy (SIRMS). LPS increased APP in non-neuronal cells as well. We conclude that Abeta deposits and hyperphosphorylated tau are also associated with type 2 diabetes, highlighting common pathogenetic features in neurodegenerative disorders, including AD and type 2 diabetes and suggesting that Abeta deposits and hyperphosphorylated tau may also occur in other organs than the brain.
Miklossy
Judith
J
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada. judithmiklossy@bluewin.ch
Qing
Hong
H
Radenovic
Aleksandra
A
Kis
Andras
A
Vileno
Bertrand
B
Làszló
Forró
F
Miller
Lisa
L
Martins
Ralph N
RN
Waeber
Gerard
G
Mooser
Vincent
V
Bosman
Fred
F
Khalili
Kamel
K
Darbinian
Nune
N
McGeer
Patrick L
PL
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010766:Phosphorylation; D014018:Tissue Distribution; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016875:tau Proteins